Puromycin effect on memory may be due to occult seizures

Intracerebral injections of puromycin, which have been shown to impair memory 3 hours after training, increase the susceptibility of mice to seizures after administration of normally subconvulsive doses of pentylenetetrazol. Cycloheximide, which antagonizes the puromycin-induced amnesia 3 hours after training, also antagonizes the puromycin effect on susceptibility to seizure. The anticonvulsant diphenylhydantoin antagonizes the puromycin effect on memory. The puromycin effect on memory may be due to occult seizures.     

Puromycin and retention in the goldfish

A first experiment compared the behavior of goldfish injected with puromycin immediately after each of a weekly series of brief discriminative training sessions in the shuttlebox to that of appropriate controls. Discrimination was not prevented, nor was escape from shock impaired, but probability of response to the conditioned stimuli, both positive and negative, was reduced substantially. These results suggest that puromycin interferes with the consolidation of conditioned fear. The null outcome of a second experiment, in which all training was given in a single long session instead of a series of short sessions, suggests (contrary to recent indications) that consolidation begins in the training session. The conditioned-fear hypothesis is supported by the results of a third experiment in which the animals were shocked upon entering a goalbox to which they had previously learned to swim for food; animals injected with puromycin, immediately after the shock, entered the goalbox more readily 1 week later than did appropriate controls.     

Actinomycin D blocks formation of memory of shock-avoidance in goldfish

When 2 micrograms of antinomycin D was injected intracranially into goldfish immediately after a training session, the formation of long-term memory of a shock-avoidance was blocked. The results are discussed in relation to similar findings with acetoxycycloheximide and puromycin in the goldfish and with apparently conflicting results in the mouse.     

Puromycin and cycloheximide: different effects on hippocampal electrical activity

Abstract. Mice were injected in the temporal region of the brain with cycloheximide or puromycin; both agents markedly inhibit protein synthesis in the brain. Recordings of electrical activity were made in the hippocampal region 5 hours after injection of these drugs. The amplitude and frequency observed in records from mice injected with cycloheximide were indistinguishable from those injected with saline alone. Records from puromycin-injected mice were strikingly abnormal. This finding may contribute to the differences in behavioral effects of intracerebral injections of the two inhibitors of protein synthesis studied.     

Memory in the Japanese quail: effects of puromycin and acetoxycycloheximide

Intracerebral injections of puromycin produced memory deficits in naive quail trained to discriminate between red and green stimuli. Puromycin aminonucleoside, acetoxycycloheximide, and saline had no such effect. After a single reversal of the visual cues, naive quail treated with puromycin performed better than control birds. Also, puromycin had no effect on performance when injected into previously trained animals. High doses both of puromycin and acetoxycycloheximide inhibited ribonucleic acid and protein synthesis to a similar extent, while low doses of puromycin inhibited only protein synthesis. Since only puromycin inhibited memory, the basis for its effect appears more likely to be mediated by the action of peptidyl-puromycin rather than by the quantitative inhibition of macromolecular synthesis or by some nonspecific toxic action.     

Memory-blocking agents: effects on olfactory discrimination in homing salmon

Homing salmon were injected intracranially with puromycin, actinomycin D, or cycloheximide. From 4 to 7 hours after such treatment these agents markedly inhibited olfactory bulbar discrimination between home water and other natural waters, including spawning sites for other groups of salmon. At longer intervals after treatment there was a partial restoration of olfactory memory-based discrimination. The dosages of the inhibitors used could be shown to have depressed incorporation of H(3)-leucine into protein by 78 percent or of H(3)-uridine into RNA by 41 percent in the salmon brains 4 hours after intracranial injection. These findings suggest that acute blockage of RNA synthesis or protein synthesis can interfere with long-term olfactory memory in anadromous salmon, at least as this function can be analyzed by electrophysiological methods. This implies that long-term olfactory memory depends upon continued metabolism of RNA and continued protein synthesis.     

Intracerebral saline: effect on memory of trained mice treated with puromycin

It was shown that puromycin administered to mice 1 or more days after maze-learning blocks expression of memory; the blockage can be removed by intracerebral injections of saline. We present evidence that intracerebral injections of saline are relatively ineffective in restoring memory when puromycin is administered either before or immediately after training; in these two situations puromycin appears to interfere with consolidation of memory.     

Memory in mice as affected by intracerebral puromycin

The antibiotic, puromycin, caused loss of memory of avoidance discrimination learning in mice when injected intracerebrally. Bilateral injections of puromycin involving the hippocampi and adjacent temporal cortices caused loss of short-term memory; consistent loss of longer-term memory required injections involving, in addition, most of the remaining cortices. Spread of the effective memory trace from the temporal-hippocampal areas to wide areas of the cortices appears to require 3 to 6 days, depending upon the individual animal. Recent reversal learning was lost while longer-term initial learning was retained after bilateral injections into the hippocampal-temporal areas.     

Benzpyrene hydroxylase induction by polycyclic hydrocarbons in hamster embryonic cells grown in vitro

Treatment of hamster embryonic cells with 1,2-benzanthracene for 4 to 48 hours induced a three- to tenfold increase in the activity of benzpyrene hydroxylase. That the increase in enzyme activity was completely prevented by puromycin suggested an induction of enzyme synthesis.     

Chondroitin sulfate: inhibition of synthesis by puromycin

Puromycin reversibly inhibits synthesis of chondroitin sulfate by vertebral chondrocytes from 10-day-old chick embryos. Treatment of these cells with puromycin for 5 hours does not affect viability or capacity to multiply on subsequent release from their matrix. It is suggested that synthesis of this polysaccharide is coupled with that of protein; there may be a feedback control in its synthesis.     

Interferon inducers in vitro: difference in sensitivity to inhbitiros of RNA and protein synthesis

Interferon can be induced by diverse agents in a variety of mammalian cell cultures through apparently two mechanisms. One results in an early (2 to 10 hours) appearance of interferon and is relatively resistant to inhibition by actinomycin, puromycin, or fluorophenylalanine. A second mechanism results in a late (18 to 24 hours) appearance of interferon and is more sensitive to inhibition by these inhibitors. The molecular basis for each mechanism is unclear. Since each interferon inducer may have multiple effects on the cell, the differences observed may not necessarily reflect a fundamental difference in the mechanism of interferon stimulation.     

Intracellular injection of cAMP induces a long-term reduction of neuronal K+ currents

Intracellular signals that trigger long-term (24-hour) changes in membrane currents in identified neurons of Aplysia have been examined in order to understand the cellular mechanisms underlying long-term sensitization. Adenosine 3',5'-monophosphate (cAMP) was directly injected into individual sensory neurons to mimic the effects of sensitization training at the single cell level. Potassium currents of these cells were reduced 24 hours after injection of cAMP; these currents were similar to those reduced 24 hours after behavioral sensitization. These results suggest that cAMP is part of the intracellular signal that induces long-term sensitization in Aplysia.     

Puromycin: action on neuronal mitochondria

Puromycin, in dosages that inhibit cerebral protein synthesis and expression of memory in mice, produces swelling of neuronal mitochondria. Acetoxycycloheximide, which inhibits cerebral protein synthesis to the same extent as puromycin, fails to produce swelling of neuronal mitochondria. Puromycin and heximide mixtures produce severe inhibition of protein synthesis, but result in a minimal swelling of neuronal mitochondria and in a decrease of peptidylpuromycin complexes to a level of 30 percent of that following the injection of puromycin alone. It is concluded that swelling of neuronal mitochondria in the presence of puromycin is not due to inhibition of cerebral protein synthesis per se, but is related to a specific action of puromycin on ribosomal protein synthesis. The findings are consistent with the hypothesis that peptidyl-puromycin complexes are responsible for mitochondrial swelling.     

End-organ effects of thyroid hormones: subcellular interactions in cultured cells

Both actinomycin D and puromycin suppress the formation of colonies by cultured human kidney epithelial cells (T-l), but inactivation by puromycin is partially reversed with thyroid hormones. Uptake by the cells of L-thyroxine labeled with iodine-125, 60 to 80 percent of which is nuclear, is depressed by actinomycin and enhanced by puromycin. Genome and possibly nuclear membrane are implicated as initiating loci.     

Puromycin analogs: action of adrenocorticotropic hormone and the role of glycogen

The effect of the injection into rats of analogs of puromycin, 6-dimethylaminopurine, and the aminonucleoside of puromycin on the stimullation of steroidogenesis by adrenocorticotropic hormone was coin pared with that of puromycin and cycloheximide. This stimulation was blocked only by the antibiotics, which also inhibited adrenal protein synthesis. Glycogenolysis is not associated with the primary mechanism of the adrenocorticotropic hormone stimnulation of steroid hormone biosynthesis in rats.     

Reticuloendothelial blockade: effect of puromycin on opsonin-dependent recovery

Reticuloendothelial blockade induced by the administration of a gelatinized "reticuloendothelial test lipid emulsion" is due to a loss of opsonic activity in the plasma. Recovery from blockade, which is associated with restoration of plasma opsonins, was inhibited by the administration of puromycin. The effect of puromycin appears to be mediated by inhibition of opsonin formation rather than a puromycin-induced macrophage defect in phagocytosis.     

Turnover of rat liver tyrosine transaminase: stabilization after inhibition of protein synthesis

Turnover of the rat liver tyrosine transaminase in vivo was measured by a label and chase procedure under conditions where the amount of enzyme undergoes no change. Half-life of the (14)C-labeled enzyme in this basal condition was found to be 1.5 +/- 0.3 hours. Inhibitors of protein synthesis (cycloheximide or puromycin) do not appreciably influence the basal enzyme level over a 5-hour period, although these drugs will block hormonal induction of this enzyme. In pulse-labeling experiments, cycloheximide blocked transaminase synthesis almost completely. The conclusion that enzyme degradation, as well as synthesis, must be blocked when protein synthesis is stopped was confirmed in experiments showing that labeled enzyme is stable in the liver of rats treated with cycloheximide The participation of a continuously synthesized polypeptide in the degradative phase of transaminase turnover is suggested.     

Temporal synergism of corticosterone and prolactin controlling gonadal growth in sparrows

Gonadal growth was controlled in two avian species by corticosterone and prolactin injected daily at various times. Testicular growth was induced in photorefractory house sparrows (Passer domesticus) kept in continuous light by prolactin injected 4 or 8 hours after administration of corticosterone. Other temporal patterns were ineffective. Gonadal growth was also stimulated in photosensitive white-throated sparrows (Zonotrichia albicollis) kept in continuous light by prolactin injected 12 hours after administration of corticosterone. Daily injections of prolactin 8 hours after injection of corticosterone inhibited gonadal growth. The seasonal cycle of reproductive photorefractoriness and photosensitivity is controlled by a changing relation between the daily rhythms of plasma concentrations of corticosterone and prolactin.     

Memory impairment after subcutaneous injection of acetoxycycloheximide

Subcutaneous injection of 240 micrograms of acetoxycycloheximide in mice rapidly produces marked inhibition of cerebral protein synthesis. Treated mice were trained to escape shock by choosing the lighted limb of a T-maze. When trained five or more minutes after injection, they had a normal capacity to learn. They remembered normally 3 hours after training, but 6 hours after training they had markedly impaired retention. Amnesia persisted thereafter. Injections immediately after training had a less marked but significant amnesic effect. These studies suggest that protein synthesis is not necessary for learning or for memory for 3 hours after training but that it is required for long-term memory. The protein synthesis which appears to be necessary for long-term e3memory occurs during training, or within minutes after training, or both.     

Hydroxyurea: suppression of two-stage carcinogensis in mouse skin

Hydroxyurea, a selective cytotoxic agent for cells in DNA synthesis, injected intraperitoneally at 24 and 48 hours after the first painting with 1 percent croton oil, significantly reduced the tumor yield in the two-stage chemical carcinlogenesis in mouse skin. A comparable group of mice receiving hydroxyurea only once at 24 hours had a tumor induction similar to that in controls.